Coccidioides genomes from low-incidence states reveal complex migration history across the western United States.

Abstract

Coccidioidomycosis (Valley fever), caused by the fungal pathogen Coccidioides, is increasing in incidence across the western United States and parts of the Americas. However, genomic data from low-incidence regions remain scarce, limiting our understanding of the pathogen's dispersal and evolution. To address this gap, we prospectively collected Coccidioides-positive clinical isolates submitted to a national diagnostic laboratory between January 2023 and November 2024. We performed whole-genome sequencing on 27 clinical isolates from Utah, Colorado, and Nevada-states with no previously available Coccidioides genomes-and sequenced an additional 22 isolates from California. For Utah patients, we also reviewed medical records to assess potential travel history. Among the 27 newly sequenced isolates, three were identified as Coccidioides immitis and 24 as Coccidioides posadasii. The C. immitis isolates, all from a single Utah patient, were linked to recent travel to southern California. In contrast, C. posadasii isolates from Utah, Colorado, and Nevada were phylogenetically diverse and dispersed across the species tree. Ancestral state reconstructions suggested multiple independent introductions: at least seven into Utah, two into Nevada, and seven into Colorado. The C. immitis clade likely originated in California (likelihood = 0.96), while C. posadasii traces to Arizona (likelihood = 0.99). These results reveal a complex dispersal history of Coccidioides in the western United States, driven by recurrent introductions rather than a single emergence event. Our study underscores the need for continued genomic surveillance in underrepresented regions to fully capture the evolutionary dynamics of this emerging fungal pathogen.IMPORTANCEValley fever is a fungal disease caused by Coccidioides species, primarily found in arid regions of the western United States and parts of Central and South America. While most genomic studies focus on high-incidence areas, the evolutionary dynamics of the fungus in low-incidence states remain poorly understood. In this study, we analyzed clinical Coccidioides isolates from Utah, Colorado, and Nevada-states with reported cases but limited genomic data. Using whole-genome sequencing and phylogenetic analysis, we found evidence of multiple introductions into each state, likely from neighboring high-incidence regions such as Arizona and California. In Utah, we detected both Coccidioides immitis and Coccidioides posadasii, though the C. immitis case was associated with recent travel. Only C. posadasii was found in Colorado and Nevada. These findings support ongoing dispersal rather than a single introduction and highlight the need for expanded genomic surveillance beyond traditionally endemic regions.